Assistant Managing Editor

Bristol-Myers Squibb Co. is planning a quick rollout of ipilimumab following its Friday approval as the first drug to demonstrate improvement in overall survival in metastatic melanoma.

The New York-based pharma firm will get the drug, branded Yervoy, to patients "in a matter of weeks," said BMS spokeswoman Jennifer Fron Mauer. "We are all ready to go."

Despite a few jitters after the FDA cancelled a highly anticipated advisory panel for the drug, the agency's nod by the March 26 PDUFA date largely had been expected. Data from the pivotal trial dubbed 020, as reported at last year's American Society of Clinical Oncology meeting and published in The New England Journal of Medicine, were solid. The drug upped overall survival at one year vs. the gp100 peptide vaccine (46 percent vs. 25 percent) and at two years (24 percent vs. 14 percent).

Plus, melanoma is a space that has racked up the failures over the years, including notable late-stage misses with Genta Inc.'s Bcl-2-targeting antisense drug Genasense (oblimersen) and tyrosine kinase inhibitor Nexavar (sorafenib) from Onyx Pharmaceuticals Inc. and Bayer AG. (See BioWorld Today, June 8, 2010.)

But the best news might be the drug's better-than-expected labeling. The 020 study had tested Yervoy in a second-line melanoma setting, but Mauer said the FDA's final labeling did not restrict use to that setting.

That means promising data released earlier last week in first-line patients could offer an immediate boost. Data from the latest study, dubbed 024, which tested Yervoy in combination with dacarbazine vs. dacarbazine alone in previously untreated metastatic melanoma patients with Stage III or Stage IV disease, showed that the drug again improved overall survival. (See BioWorld Today, March 23, 2011.)

The National Cancer Institute has reported that about 68,000 new cases of melanoma were diagnosed in the U.S. last year, and roughly 8,700 people died from the disease in 2010.

Given that it's the first melanoma drug to show a clear survival benefit, analysts are anticipating a quick uptake of the drug. BMS has priced Yervoy at about $120,000 – $30,000 per each 3 mg/kg infusion given over three months. An immunotherapy, Yervoy is "a little different than other drugs that are given until disease progression," Mauer told BioWorld Today.

Yervoy is designed to work as a T-cell potentiator, blocking CLTA-4, a T-cell molecule that regulates immune responses. Rather than directly attacking the tumor, it suppresses CTLA-4, allowing the body's immune system to mount a sufficient T-cell response to the tumor. "We found that four infusions given over three months were effective in stimulating the body's immune system," Mauer said.

Yervoy is being approved with a risk evaluation and mitigation strategy. In studies, severe to fatal autoimmune reactions were seen in 12.9 percent of patients.

The drug initially was discovered at Princeton, N.J.-based Medarex Inc., which partnered ipilimumab with BMS in 2004. At that time, Yervoy had started Phase III testing. In 2007, the firms reported disappointing data from three pivotal studies designed to measure response rate, but decided the next year to amend the Phase III program to measure overall survival, a more effective endpoint for immunotherapies. (See BioWorld Insight, March 28, 2011.)

BMS bought out Medarex in 2009, paying $2.4 billion. (See BioWorld Today, July 24, 2009.)

Whether Yervoy's approval will herald more wins for the melanoma space remains to be seen. But there are some promising candidates. PLX4032, from Plexxikon Inc. (which is being acquired by Daiichi Sankyo Co. Ltd.) and partner Roche AG has shown stunning data in melanoma patients with BRAF mutations, and the firms expect to file for regulatory approval this year. (See BioWorld Today, Jan. 20, 2011.)

Other drugs in late-stage development include a cancer vaccine, Allovectin-7, from San Diego-based Vical Inc., which is in Phase III as a first-line therapy for patients with Stage III and Stage IV recurrent metastatic melanoma and OncoVex GM-CSF, which is in pivotal testing in melanoma. OncoVex GM-CSF is being developed by BioVex Inc., of Woburn, Mass., which was just acquired by Thousand Oaks, Calif.-based Amgen Inc.

And last year, Swiss firm Debiopharm Group agreed to co-develop anti-CTLA-4 antibody tremelimumab with Pfizer Inc. That drug had been halted after interim Phase III data showed it likely would not meet statistical significance, but Debiopharm is hoping the use of an undisclosed biomarker will make the difference. (See BioWorld Today, Jan. 8, 2010.)

In addition to U.S. approval, BMS also is seeking a European nod for Yervoy. A marketing authorization application is under review.

Beyond melanoma, the pharma firm plans to expand ipilimumab into other solid tumor indications. Mauer said the drug is being tested in a Phase III trial in prostate cancer and is set to start another Phase III trial in lung cancer. The drug is in earlier-stage development in other tumor types.